• 研究方向

    Research Direction

    翻译起始因子eIF3

    TRANSLATION INITIATION FACTOR eIF3

    我们关注eIF3在翻译起始、延伸和抑制中的典型和非典型作用，尤其对揭示eIF3在翻译、代谢和能量平衡中的特殊作用感兴趣。在过去三年的研究中，eIF3在mRNA翻译中的作用得到了广泛延伸。现在看来，这种多亚基复合物参与了mRNA翻译的每一种可能形式，控制着蛋白质合成的每一个步骤，如从起始到延伸再到蛋白质的质量控制。通过eIF3的研究，我们开始认识到蛋白质合成是一个高度集成的过程，它与蛋白质的合成、蛋白质的折叠、亚细胞靶向和降解相互协调。与此同时，eIF3亚基似乎在不同组织和单个细胞之间可能具有不同的特定功能。然而，关于eIF3在蛋白质合成中的亚基和组织特异性功能、以及它们受环境条件和翻译后修饰的调节作用，还需要做更深的了解。

    We are focusing on canonical and non-canonical roles of eIF3 in translation initiation, elongation, and repression. In particular, are interested in revealing the specific role of eIF3 in translation, metabolism, and energy balance. Studies over the past three years have substantially expanded the involvements of eIF3 in mRNA translation. It now appears that this multi-subunit complex is involved in every possible form of mRNA translation, controlling every step of protein synthesis from initiation to elongation, termination, and quality control in positive as well as negative fashion. Through the study of eIF3, we are beginning to appreciate protein synthesis as a highly integrated process coordinating protein production with protein folding, subcellular targeting, and degradation. At the same time, eIF3 subunits appear to have specific functions that probably vary between different tissues and individual cells. Much remains to be learned, however, about subunit and tissue-specific functions of eIF3 in protein synthesis and their regulation by environmental conditions and posttranslational modifications.

    蛋白质内稳态

    PROTEIN HOMEOSTASIS

    我们也在解决应激反应与蛋白质质量控制通路之间相互反应的这一难题。我们尤其感兴趣的是通过蛋白酶而实现蛋白质合成与降解的连接机制。我们发现翻译启始因子eIF3复合体与质量控制机制有关，它可能是通过核糖体与蛋白质的直接相互作用来实现的。目前，我们正在做一系列基因与生物化学的相关实验来揭示eIF3在蛋白质质量控制中所起的作用。

     

    We are also addressing the interaction of stress response and protein quality control pathways. In particular, we are interested in the coupling of protein synthesis and degradation by the proteasome. We have discovered that the translation initiation factor eIF3 complex is involved in this control, probably through direct interactions with ribosomes and the proteasome. We are performing genetic and biochemical experiments to unravel the role of eIF3 in protein quality control.

  • Publications

    Han, B.; Zhang, S.; Zhang, Y.; Yu, B.; Lin, W.; Cheng, Y.; Duan, H.; Wolf, D. A. (2025). 5' UTR-mediated retention of eIF3 on 80S ribosomes promotes co-translational folding of ER memberane proteins. Cell Reports 44(12):116662
    Duan, H., Zhang, S., Zarai, Y., Öllinger, R., Wu, Y., Sun, L., Hu, C., He, Y., Tian, G., Rad, R., Kong, X., Cheng, Y., Tuller, T., & Wolf, D. A. (2023). eIF3 mRNA selectivity profiling reveals eIF3k as a cancer-relevant regulator of ribosome content. The EMBO journal, 42(12), e112362

    Hu, C., Lin, W., Zhao, K., Tian, G., Kong, X., Luo, G., Wolf, D. A., & Cheng, Y. (2023). NDC80 status pinpoints mitotic kinase inhibitors as emerging therapeutic options in clear cell renal cell carcinoma. iScience 26(4), 106531

    Jain S, Hu C, Kluza J, Ke W, Tian G, Giurgiu M, Bleilevens A, Campos AR, Charbono A, Stickeler E, Maurer J, Holinski-Feder E, Vaisburg A, Bureik M, Luo G, Marchetti P, Cheng Y, Wolf DA. (2022) Metabolic targeting of cancer by a ubiquinone uncompetitive inhibitor of mitochondrial complex I. Cell Chem Biol 29(3):436-450

    Tian, G. Y.; Hu, C.; Yun, Y.; Yang, W.; Dubiel, W.; Cheng, Y.; Wolf, D. A. (2021) Dual roles of HSP70 chaperone HSPA1 in quality control of nascent and newly synthesized proteins. THE EMBO JOURNAL 40(13):e106183

    Wang, J.; Dubiel, D.; Wu, Y.; Cheng, Y.; Wolf, D.A.; Dubiel, W. (2021) CSN7B defines a variant COP9 signalosome complex with distinct function in DNA damage response. Cell Reports 34(4):108662

    Lin, Y.Y.; Li, F.; Huang, L.; Polte, C.; Duan, H.; Fan, J.; Sun, L.; Xing, X.; Tian, G.; Cheng, Y.; Ignatova, Z.; Yang, X.; Wolf, D.A. (2020) eIF3 associates with 80S ribosomes to promote early translation elongation, mitochondrial homeostasis, and skeletal muscle health. Molecular Cell 79(4):575-587

    Wolf, D.A.; Lin, Y.Y.; Duan, H.; Cheng, Y. (2020) eIF-Three to tango: Emerging functions of translation initiation factor eIF3 in protein synthesis and disease. J. Molecular Cell Biology 12(6), 403-409

    Sanchez, M.; Lin, Y.Y.; Yang, C.-C.; McQuary, P.; Campos, A.R.; Aza-Blanc, P.; Wolf, D.A. (2019) Crosstalk between eIF2α and eEF2 phosphorylation pathways optimizes translational arrest in response to oxidative stress. iScience 20:466-480

    Ekholm-Reed, S.; Baker, R.; Campos, A.R.; Stouffer, D.; Henze, M.; Wolf, D.A.; Loring, J.F.; Thomas, E.A.; Reed, S.I.; (2019) Reducing Mcl-1 gene dosage induces dopaminergic neuronal loss and motor impairments in Park2 knockout mice, Communications Biology 2:125

    Sanchez, M.; Xia, Z.; Rico-Bautista, E.; Cao, X.; Cuddy, M.; Castro, D.J.; Correa, R.G.; Chen, L.; Yu, J.; Bobkov, A.; Ruvolo, V.; Andreeff, M.; Oshima, R.G.; Matsuzawa, S.-I.; Reed, J.C.; Zhang, X.-K.; Hansel, D.; Wolf, D.A.; Dawson, M.I. (2018) Oxidized analogs of di(1H-indol-3-yl)methyl-4-substituted-benzenes are UPR-inducers with potent and safe anti-cancer activity. Oncotarget 10.18632/oncotarget.25285

    Dubiel, W.; Dubiel, D.; Wolf, D.A.; Naumann, M. (2018) Cullin 3-based ubiquitin ligases as master regulators of mammalian cell differentiation. Trends in Biochemical Sciences 43:95-107

    Straube, R.; Shah, M.; Flockerzi, D.; Wolf, D.A. (2017) Trade-off and flexibility in the dynamic regulation of the cullin-RING ligase repertoire. PLOS Computational Biology 13: e1005869

    Wolf, D.A.; Bahler, J.; Wise J.A. (2017) Schizosaccharomyces pombe polysome profile analysis and RNA purification. - CSH 10.1101/pdb.prot091637

    Attali, I.; Tobelaim, W.S.; Persaud, A.; Motamedchaboki, K.; Simpson-Lavy, K.J.; Mashahreh, B.; Levin-Kravets, O.; Keren-Kaplan, T.; Pilzer, I.; Kupiec, M.; Wiener, R.; Wolf, D.A.; Rotin, D.; Prag, G. (2017) Ubiquitylation-dependent oligomerization regulates activity of Nedd4 ligases. EMBO Journal 36:425-440

    Shah, M.; Su, D.; Scheliga, J.S.; Pluskal, T.; Boronat, S.; Motamedchaboki, K.; Campos, A.R.; Qi, F.; Yanagida, M.; Wolf, D.A. (2016) A transcript-specific eIF3 complex mediates global translational control of energy metabolism. Cell Reports 16:1891-1902

    Fan, J.B.; Arimoto, K.-I.; Motamedchaboki, K.; Yan, M.; Wolf, D.A.; Zhang, D.-E. (2015) Identification and characterization of a novel ISG15-ubiquitin mixed chain and its role in regulating protein homeostasis. Scientific Reports 5:12704

    Yang, C.-C.; Fazli, L.; Loguercio, S.; Zharkikh, I.; Aza-Blanc, P.; Gleave, M.E.; Wolf, D.A. (2015) Downregulation of c-SRC kinase CSK promotes castration resistant prostate cancer and pinpoints a novel disease subclass. Oncotarget 26:22060-22071

    Wolf, D.A. (2014) Is reliance on mitochondrial respiration a "chink in the armor" of therapy-resistant cancer? Cancer Cell 26, 788-795

    Yang, C.-C.; Chung, A.; Brill, L.M.; Williams, R.; Wolf, D.A. (2014) Systems analysis of the prostate tumor suppressor NKX3.1 supports roles in DNA repair and luminal cell differentiation. F1000Research 3:115
    Rico-Bautista, E.; Zhu, W.; Kitada, S.; Ganapathy, S.; Lau, E.; Krajewski, S.; Ramirez, J.; Bush, J.A.; Yuan, Z.; Wolf, D.A. (2013) Small molecule-induced mitochondrial disruption directs prostate cancer inhibition via unfolded protein response signaling. Oncotarget 4, 1212-1229

    Wu, S..; Zhou, W.; Nhan, T.; Toth J.I.; Petroski, M.D.; Wolf, D.A. (2013) CAND1 controls in vivo dynamics of the cullin 1-RING ubiquitin ligase repertoire. Nature Communications 4, 1642

    Xia, Z.; Cao, X.; Rico-Bautista, E.; Yu, J.; Chen, L.; Chen, J.; Wolf. D.A.; Zhang, X.-K.; Dawson, M.I. (2013) Relative impact of 3- and 5-hydroxyl groups of cytosporone B on cancer cell viability. Medicinal Chemistry Communications 4: 332-339

    Rico-Bautista, E.; Wolf, D.A. (2012) Skipping Cancer: Small Molecule Inhibitors of SKP2-Mediated p27 Degradation. Chemistry & Biology 19, 1497-1498 (Preview invited)

    Bauer, F.; Matsuyama, A.; Candiracci, J.; Dieu, M.; Scheliga, S.; Wolf, D.A.; Yoshida, M.; Hermand, D. (2012) Translational control of cell division by elongator. Cell Reports 1, 424-433

    Lackner, D.H.; Schmidt, M.W.; Wu, S.; Wolf, D.A., Bähler, J. (2012) Regulation of transcriptome, translation, and proteome in response to environmental stress in fission yeast. Genome Biology 13:R25

    Keren-Kaplan, T.; Attali, I., Motamedchaboki, K.; Davis, B.A.; Tanner, N., Reshef, Y., Laudon, E.; Kolot, M.; Levin-Kravets, O.; Kleifeld, O.; Glickman, M.; Horazdovsky, B.F.; Wolf, D.A., Prag, G. (2012) Synthetic biology approach to reconstituting the ubiquitylation cascade in bacteria. EMBO J.31, 378 - 390

    Petroski, M.D.; Salvesen, G.S.; Wolf, D.A. (2011) Urm1 couples sulfur transfer to ubiquitin-like protein function in oxidative stress. Proc. Natl. Acad. Sci. USA, 108, 1749-1750 (Commentary, invited)

    Rico-Bautista, E.; Yang, C.-C.; Lu, L.; Roth, G.P.; Wolf, D.A. (2010) Chemical genetics approach to restoring p27Kip1 reveals novel compounds with antiproliferative activity in prostate cancer cells. BMC Biology 8:153

    Sha, Z.; Brill, L.M.; Cabrera, R.; Kleifeld, O.; Glickman, M.H.; Chang, E.C.; Wolf, D.A. (2009) The eIF3 Interactome Reveals the Translasome, a Supercomplex Linking Protein Synthesis and Degradation Machineries. Molecular Cell 36, 141-152

    Schmidt, M.W.; McQuary, P.R.; Wee, S.; Hofmann, K.; Wolf, D.A. (2009) F-box-directed CRL complex assembly and regulation by the CSN and CAND1. Molecular Cell 35,586-597

    Wu, S.; Wolf, D.A. (2009) Destruction of RhoA CULtivates Actin. Molecular Cell 35, 735-736 (Preview, invited)
    Jones, M.R.; Quinton, L.J.; Blahna, M.T.; Neilson, J.R.; Fu, S.; Ivanov, A.R.; Wolf, D.A.; Mizgerd, J. (2009) Zcchc11-dependent uridylation of microRNA directs cytokine expression . Nature Cell Biology 11, 1157-1163

    Yang, C.-C.; Wolf, D.A. (2009) Inflamed Snail speed metastasis. Cancer Cell 15, 355-357 (Preview, invited)

    Wolf, D.A.; Petroski, M.D. (2009) Rfu1, stimulus for the ubiquitin economy. Cell 137, 397-398 (Preview, invited)

    Brill, L.M.; Motamedchaboki, K.; Wu S.; Wolf, D.A. (2009) Comprehensive proteomic analysis of Schizosaccharomyces pombe by two-dimensional HPLC-tandem mass spectrometry. Methods 48, 311-319

    Herzinger, T.; Wolf, D.A. (2009) Snail puts melanoma on the fast track. Pigment Cell and Melanoma Research 22, 150-151

    Schmidt, M.W.; Houseman, E.A.; Ivanov, A.R; Wolf, D.A. (2007) Comparative proteomic and transcriptomic profiling of the fission yeast Schizosaccharomyces pombe. Molecular Systems Biology, 3:79

    Zhou, C.; Arslan, F.; Wee, S.; Krishnan, S.; Ivanov, A.R.; Oliva, A.; Leatherwood, J.; Wolf, D.A. (2005) PCI proteins eIF3e and eIF3m define distinct translation initiation factor 3 complexes. BMC Biology, 3:14

    Wee, S.; Geyer, R.; Toda, T.; Wolf, D.A. (2005) CSN facilitates cullin-RING ubiquitin ligase function by counteracting autocatalytic adapter instability. Nature Cell Biology 7, 387-391 (Full text not freely available, please see pre-publication history for final author manuscript)

    Doud, M.K.; Schmidt, M.W.; Hines, D.; Naumann, C.; Kocourek, A.; Kashani-Poor, N.; Zeidler, R.; Wolf, D.A. (2004) Rapid prefractionation of complex protein lysates with centrifugal membrane adsorber units improves the resolving power of 2D-PAGE-based proteome analysis. BMC Genomics 5:25

    Wolf, D.A.; Wee, S.; Zhou, C. (2003) The COP9 signalosome: an assembly and maintenance platform for cullin ubiquitin ligases? Nature Cell Biology 5, 1029-1033 (Full text not freely available, please see pre-publication history for final author manuscript)

    Schmidt, M.; Jain, A.; Wolf. D.A. (2003) Multidimensional proteomic analysis of proteolytic pathways involved in cell cycle control. In: Cell Cycle Checkpoint Control Protocols. Lieberman H. B. ed. New York: Humana Press (2003) Vol. 241: 235-245

    Geyer, R.; Wee, S.; Anderson, S.; Yates J.R.III; Wolf. D.A. (2003) BTB/POZ domain proteins are putative substrate adaptors for cullin 3 ubiquitin ligases. Molecular Cell 12, 783-790

    Wolf, D.A.; Geyer, R. (2003) Dynamic release of Cdc34 from SCF: The hand that rocks the cradle. Cell 114, 532-533 (Preview, invited)

    Zhou, C.; Wee, S.; Rhee, E.; Naumann, M.; Dubiel, W.; Wolf, D.A. (2003) Fission yeast COP9/signalosome suppresses cullin activity through recruitment of the deubiquitylating enzyme Ubp12p. Molecular Cell 11, 927-938

    Wee, S.; Hetfeld, B.; Dubiel, W.; Wolf, D.A. (2002) Conservation of the COP9/signalosome in budding yeast. BMC Genetics 3:15

    Lu, L.; Schulz, H.; Wolf, D.A. (2002) The F-box protein SKP2 mediates androgen control of p27 stability in LNCaP human prostate cancer cells. BMC Cell Biology 3:22

    Seibert, V.; Prohl, C.; Schoultz, I.; Rhee, E.; Lopez, R.; Abderazzaq, K.; Zhou, C.; Wolf, D.A. (2002) Combinatorial diversity of fission yeast SCF ubiquitin ligases by homo- and heterooligomeric assemblies of the F-box proteins Pop1p and Pop2p. BMC Biochemistry 3:22

    Zhou, C.; Seibert, V.; Geyer, R.; Rhee, E.; Lyapina, S.; Cope, G.; Deshaies, R.J.; Wolf, D.A. (2001) The fission yeast COP9/signalosome is involved in cullin modification by ubiquitin-related Ned8p. BMC Biochemistry 2:7

    Lyapina, S.; Cope, G.; Shevchenko, A.; Serino, G.; Tsuge, T.; Zhou, C.; Wolf, D. A.; Wei, N.; Shevchenko, A.; Deshaies, R. J. (2001). Promotion of NEDD8-CUL1 conjugate cleavage by COP9 signalosome. Science 292, 1382-1385 (Free upon registration)

  • Lab Members

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    Dieter A. Wolf


    Professor, Westlake University

    1987~1995 M.D. Degree, Ludwig-Maximilians University Munich, Germany
    1992~1994 Independent research, Helmholtz Center Munich, Germany
    1994~1996 Postdoctoral Associate, Harvard Medical School
    1996~1998 Postdoctoral Associate, Stanford University School of Medicine
    1998~2007 Assistant/Associate Professor, Harvard School of Public Health
    2007~2019 Professor, Burnham Institute
    2015~2022 Distinguished Professor, Xiamen University, China
    2019~2022 Resident & Medical Head, Biomarker Program, Medical Genetics Center Munich
    2021~present Adjunct Group Leader, Technical University Munich
    2023~present Professor, Westlake University

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    Haoran Duan


    Ph.D., Biochemistry, Xiamen University

    M.SC., Biochemistry, Xiamen University

    B.SC., China Pharmaceutical University

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    Cheng Hu


    Ph.D., Biochemistry, Xiamen University

    M.SC., Biochemistry, Xiamen University

    B.SC., Guizhou University

     

     

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    Fajin Li


    Ph.D., Tsinghua University

    B.SC., Tianjin Medical University

     

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    Reza Mohammadinejad

    Ph.D., Biomedical Sciences, Kerman University of Medical Sciences

    M.Sc., Biotechnology, Graduate University of Advanced Technology

    B.Sc., Plant Protection, Vali-e-Asr University

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    Mengyu Li


    (class of 2021)

    M.SC., Biology, New York University, NY, USA

    B.SC., Sichuan University, Chengdu, China

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    Xingjian Dong


    (class of 2022)

    B.SC., Huazhong Agricultural University

     

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    Changyi Shi


    (class of 2022)

    M.Med Zhejiang Laboratory of Animal Center, Hangzhou Institute of Medicine Chinese Academy of Sciences
    B.S China Pharmaceutical University

     

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    Yang Wu


    (class of 2023)

    M.SC The State University of New York, Stony Brook, NY, USA

    B.EN Southeast University, China

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    Fanglin Luo


    (class of 2023)

    B.SC., Shenyang Pharmaceutical University

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    Mangze Hu


    (class of 2023)

    M.SC., Immunology, Nantong University

    B.SC., Anhui University of Chinese Medicine

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    Tongtong Ba


    (class of 2023)

    M.SC.,Huazhong Agricultural University

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    Zihan Wang


    (class of 2024)

    B.SC.,Zhejiang University

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    Dan Su


    PhD student of Technical University of Munich

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    Yang Xiao


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    Huihong Li


    M.SC., Henan Agriculture University, China

     

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    Bin Wei


    M.SC., Henan Agriculture University, China
    B.SC., Henan University of Animal Husbandry and Economy, China

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    Luhao Yang



    B.SC., Hainan University ,China

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    Siqiong Zhang

    Research assistant & Lab manager (2023~2025)
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    Baochun Han
    PhD student (2019~2025)

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    Jing Wang

    Postdoctoral researcher (2023~2025)

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    Danning Dai, Research assistant (2023~2024),

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    Yixian Qin, Research assistant (2023~2024),

     

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    Shuhan Shi, Administrative Assistant (2022~2024),

     

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    Weimin Lin, Master Student (2020~2023),

    now Laboratory technician at Sahnghai Xihua Co., Ltd

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    Yurui Zhang, Master Student (2019~2022),

    now PhD at Chinese Academy of Medical Sciences

     


     

     

     

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    Ran Liu, master student (2018~2021),

    now manager of Guangzhou Pharmaceutical Co., Ltd.

     

    Kemeng Zhao, master student (2018~2021),

    now working at Center of Disease Control and Prevention at Xiuzhou district, Jiaxing City.

     

    Yun Yun, master student (2018~2021),

    now working at Organisation Department of Jiangsu Provincial Party Committee.

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    Guiyou Tian, PhD Student (2016~2021),

    now Lecturer at Gannan Normal University

     

     

     

     

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    Linlu Huang, master student (2017~2020),

    now patent examiner at Fujian Sub-centre of Patent Examination Collaborative Centre

     

    Wei Ke,master student (2017~2020),

    now working at Statistics bureau at Chuzhou City

     

    Yanmeng Wu, master student (2017~2020),

    now working at Shanghai Tenth Hospital

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    Dan Su, master student (2014~2017),

    now PhD student at Technical University of Munich

     

    Yingying Lin, PhD student (2015~2019),

    now Assistant professor at Hangzhou Normal University

     

    Xiaosong Liu, master student (2016~2019),

    now PhD student at Intersectional Research Centre for Biology and Chemistry, Shanghai Institute of Organic Chemistry, CAS

     

    Li Sun, master student (2016~2019),

    now Thematic Head of Pharmacology at Zhaoyan New Drug Research and Development Centre

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    Warm Lab Family

    Work together!

    Study together!

    Make progress together!

    Together we make the world!

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    Our research benefits from global collaborators!

    Min-Min Luo, CIBR Beijing

    Long Zhou, Zhejiang University

    Yaser Hashem, University of Hamburg

    Changchun Xiao, Scripps Research Institute

    Michal Shapira, Ben-Gurion University

    Roland Rad, Technical University of Munich

    Tamir Tuller, Tel-Aviv University

    Arkadii Vaisburg, Crocus Laboratories Inc

    Matthias Bureik, Tianjin University

    Reiko Sugiura, Kindai University

    Zoya Ignatova, University of Hamburg

    Wolfgang Dubiel, Charite University Hospital

    Xuerui Yang, Tsinghua University

    Yabin Cheng, Xiamen University

  • Contact Us

    Professor Dieter A. Wolf 
    E-mail：dawolf@westlake.edu.cn
    Address：No.18 Shilongshan Road Cloud Town,Xihu District, Hangzhou, Zhejiang PR China
    Post code：310024
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